norvancomycin and Bacterial-Infections

Antibacterial spectrum and activity of norvancomycin are comparable with vancomycin, and it has been widely used in China. Norvancomycin can penetrate into the cerebrospinal fluid (CSF) through the damaged blood-brain barrier in patients after craniotomy. Because higher inter-individual variability was observed, we aimed to identify factors related to drug concentration to guide clinicians with norvancomycin dosing.. After craniotomy, patients with an indwelling catheter in the operational area/ventricle were intravenously administered norvancomycin. Venous blood and CSF specimens were collected at a scheduled time for measuring drug concentrations. Blood and CSF data were fitted simultaneously with the use of the nonlinear fixed-effects modeling method to develop the population pharmacokinetic model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic parameters. A model-based simulation was performed to find optimized regimens for different subgroups of patients.. A 3-compartmental model (central, peripheral, and CSF compartments) with 2 elimination pathways (drug elimination from the kidney and CSF outflow) was developed to characterize the in vivo process of norvancomycin. The covariate analysis identified that weight and drainage amount were strongly associated with the central volume and the drug clearance from CSF, respectively. Goodness-of-fit and model validation suggested that the proposed model was acceptable. A dosage regimen table was created for specific patient populations with different weights and drainage amounts to facilitate clinical application.. We identified 2 clinical markers associated with plasma and CSF concentrations. The proposed simulation may be useful to clinicians for norvancomycin dosing in this specific population with normal kidney function.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Body Weight; Craniotomy; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Models, Biological; Vancomycin; Young Adult

In this paper, population pharmacokinetics (PPK) and pharmacodynamics of norvancomycin in patients were investigated. The studied dataset was derived from 146 patients with confirmed or suspected gram-positive bacterial infections, as well as 20 healthy volunteers. A PPK model was developed and validated by the nonlinear mixed effect model (NONMEM) software. The norvancomycin minimum inhibitory concentrations (MICs) for the isolates from patients were determined by the agar dilution method. The best model was a two-compartment pharmacokinetic model with exponential inter-individual error and an additive residual error statistic model. The findings of the present study indicated that the change in CLcr values had different effects on drug clearance (CL). In patients with renal dysfunction (CLcr< or =85 ml/min), CL (L/h)=2.54.(CLcr /50)1.20, while in patients with normal renal function (CLcr>85 ml/min), CL=6.0.(WT/60)0.52. An increased volume of peripheral distribution (V2) was observed when norvancomycin was co-administered with diuretics. Inter-individual variability in CL, V1, Q, and V2 was 35.92%, 11.40%, 0, and 79.75%, respectively. Residual variability was 3.05 mg/L. The logistic stepwise analyses revealed that only the ratio of AUC24 /MIC was a major factor which could significantly predict the clinical outcome and bacterial eradication in patients. As the AUC24/MIC ratio was >579.90 for staphylococcal infection and >637.67 for enterococcal infections, approximately 95% of patients would be predicted to achieve a cured clinical outcome. In conclusion, AUC24/MIC should be a major pharmacokinetics/pharmacodynamics (PK/PD) parameter to predict the clinical efficacy of norvancomycin. An optimized regimen of norvancomycin can be simulated and developed for different subgroups of patients who have special physiologic and pathologic conditions.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Computer Simulation; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Vancomycin

To investigate the safety of norvancomycin, and provide basis for its rational use in clinical practice.. We documented all adverse events occurred in inpatients who receive intravenous infusion of norvancomycin, then we evaluated the relationship between adverse events and norvancomycin and calculated the rates of adverse reaction.. 1031 patients were enrolled in this study from March 2002 to June 2003 and 965 of them could be evaluated. 80 adverse reactions occurred in 965 patients who received norvancomycin, giving a total adverse reaction rate of 8.29%. The systemic adverse reactions included renal impairment (4.04%), hepatic impairment (2.38%) and allergic reaction (1.76%). 15 patients discontinued the treatment because of the adverse reaction. The rates were higher in patients who use other antimicrobial agents concomitantly or whose age >/= 60 years. The rates of renal impairment were higher in those with age >/= 60 years, and the rates of hepatic impairment were higher in whose received this agent longer than 14 days. These factors were independent risk factors (P < 0.05).. The overall adverse reaction rate of norvancomycin was low. A few patients experienced drug-related reaction, most of these adverse reactions were mild and tolerable. The adverse reactions tended to occur in older patients, those who use other antibiotic concomitantly or those who receive this agent longer than 14 days.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Female; Humans; Infant; Infusions, Intravenous; Male; Middle Aged; Vancomycin